ChemInform Abstract: A Robust and General Protocol for the Lewis‐Base‐Catalyzed Reaction of Alcohols and Alkyl Propiolates.

Unified Approach to Furan Natural Products via Phosphine‐Palladium Catalysis

“…While conditions A1 delivered the aryl‐containing trisubstituted furans 3 y , 3 bb , and 3 gg in good yields, they failed for di‐ or trialkyl‐substituted substrates. Because conditions A worked well for the preparation of furans containing at least one electron‐withdrawing group, we attempted to make the Michael acceptor more electron‐deficient (Supporting Information, Scheme S5), but detected no product and obtained copious amounts of polymerized Michael acceptor [17c] . Intrigued by Fu's report on the use of air‐stable trialkylphosphonium salts for various cross‐couplings of deactivated aryl chlorides and bromides, [24] we adapted those conditions for our Michael–Heck reaction [Eq.…”

“…We found, however, that employing PMe 3 resulted in the rapid polymerization of methyl propiolate. Tejedor's insightful report on Lewis base‐catalyzed addition of primary, secondary, and tertiary alcohols onto alkyl propiolates suggested that the increased basicity of a tertiary alcohol, as well as the decreased nucleophilicity of the corresponding tertiary alkoxide, made it unable to compete with the dimerization or polymerization of alkyl propiolates in the presence of amines or phosphine catalysts [17c] . To remedy this quandary, we positioned a p K a ‐lowering CF 3 ‐substituent onto the tertiary alcohol [47] .…”

“…( Z )‐3‐Halo‐2‐propen‐1‐ols are versatile substrates that can be obtained rapidly and stereoselectively from readily available propargyl alcohols and alkynoates through hydro/carbometalation‐iodinolysis and hydroiodination‐reduction sequences, respectively [16] . Having both hydroxyl and vinyl halide functionalities, we have found that they can be integrated seamlessly into sequential phosphine‐palladium catalysis, wherein initially the OH group undergoes phosphine‐catalyzed ( E )‐selective Michael addition to activated alkynes to give vinyl ether intermediates, [17a–c] which then undergo sequential Heck cyclization and spontaneous aromatization to give highly substituted furans (Scheme 1 B). The phosphine organocatalyst for the Michael addition acts as a ligand in the Heck reaction.…”